General practice management of type 2 diabetes


Insulin
×
☰ Table of contents


Clinical context


The impact of insulin on microvascular and cardiovascular outcomes has been partly evaluated in a comparative prospective outcome trial (eg the United Kingdom Prospective Diabetes Study [UKPDS]).

In terms of glycaemic control in type 2 diabetes, rapid-acting insulin and long-acting insulin analogues offer little benefit relative to conventional insulins.135 However, a meta-analysis has demonstrated reduced hypoglycaemia with glargine insulin when compared to isophane insulin.136 The Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial demonstrated no beneficial or detrimental effect of glargine insulin on cardiovascular events.121

The use of insulin can improve glycaemic control in most people, but the increased risk of hypoglycaemia and weight gain (especially prandial insulins) must be considered.

Further long-term, high-quality prospective outcome studies of all glucose-lowering agents including insulin analogues are required. Improvements in surrogate markers such as HbA1c may not necessarily equate with longer term, clinically significant benefits.

Side effects of insulin therapy

Rare adverse events associated with the use of insulin have been reported in observational studies. Such events include congestive heart failure, oedema, lipodystrophy, allergic reactions, reversible transaminitis, reversible nephrotic syndrome and ß-cell destruction.61

Common side effects include hypoglycaemia and weight gain.

Risk factors for hypoglycaemia include:

  • inappropriate dose
  • timing or type of insulin (refer to below)
  • missing meals
  • alcohol intake
  • exercise
  • weight loss
  • treatment with agents potentiating hypoglycaemia (eg sulphonylureas)
  • decreased insulin clearance (eg renal failure).

Strategies for preventing hypoglycaemia in patients involve educating them about hypoglycaemic symptoms, structured SMBG, discussing and individualising glycaemic goals, and continued team-based support.61

Weight gain is variable on initiation of insulin and may accompany initial titration such that weight gain may eventually level off. Slower titration has been accompanied by slower weight gain. Strategies to address weight include: referral to an APD, management of any accompanying depression, a review of medications that may contribute to weight gain and advice on increased physical activity.

Early insulin intervention

Guidelines outlining the use of insulin in acute hyperglycaemic emergencies (including ketosis inducing and hyperosmolar crises) are available.,sup>137–139 The use of insulin in these cases may be life saving and re-assessment of long-term use can occur on metabolic stabilisation.

Insulin types

Refer to Appendix G. Types of insulin available.

Insulin delivery options

A range of devices are available to deliver insulin, including insulin injectors (pens), insulin syringes and insulin pumps. Choice will depend on patient preference and capability. A CDE or a diabetes nurse practitioner can assist in the provision of patient support.

Insulin injectors (pens) are the most common way of administering insulin as they make multiple daily injection schedules much easier and allow people to be more flexible in their self management. Some people may find the ‘InnoLet’ injector easier to use because it is larger and has more visible markings; however, there are limited forms of insulin available with this device.

Insulin pumps have traditionally only been used in the management of type 1 diabetes. There is no evidence of the beneficial effects of using insulin pumps in people with type 2 diabetes.

Single use of pen needles and syringes is recommended.


In practice


Insulin therapy can be well managed in general practice.

GPs should anticipate and proactively address the patient’s (and their own) reluctance to starting insulin therapy. Many patient concerns can be easily alleviated.140

Insulin is still the most effective glucose-lowering agent for type 2 diabetes, and can be titrated to suit the individual patient’s requirements. Commencement should not be delayed if hyperglycaemia and symptoms cannot be adequately controlled by a patient’s existing treatments. Insulin is not the end of the road for the person with diabetes, nor does it represent therapeutic or patient failure. The potential need for insulin should be broached early with patients.

When should patients start insulin?

It is important to discuss with patients with diabetes that insulin may be used at some point in their illness. Insulin should be initiated in patients with type 2 diabetes who are taking maximal doses of oral glucose-lowering agents and who have suboptimal glycaemic control (HbA1c or blood glucose above individualised target) whether they are asymptomatic96,105,141,142 or symptomatic.96

Insulin therapy may remain an alternative for elderly or nursing home patients with HbA1c >75 mmol/mol (9%), especially if control of symptomatic hyperglycaemia  is difficult.

Before starting insulin

Ensure that other possible causes of hyperglycaemia have been addressed (eg lifestyle, non-adherence to oral glucose lowering agents, taking other medication or medical conditions).141

Discuss with patients the benefits and costs of using insulin for better glycaemic control (Box 4).

Insulin initiation requires planning for patients (or their carers) with a focus on self management through education about dose adjustment, insulin delivery techniques, and SMBG and sick day management. Referral is recommended to a CDE prior to commencing insulin therapy. Insulin therapy requires initial education and skills training, with regular structured follow-up on such topics as: dose adjustment, insulin needle length and rotation techniques, hypoglycaemia management, exercise, illness and travel considerations, sharps disposal, identification, roads and maritime services  notifications, and sick day management.

Box 4. benefits and costs

Benefits

Complications
Quality of life
 

Costs

Weight
Hypoglycaemic risk
GP visits

 

Initiating insulin

All insulins work effectively140 and there is no wrong choice when commencing insulin. At the same time as selecting the insulin preparation, consider which injecting device is most suitable for the patient.
Select one of two insulin schedules:

  • Basal insulin (eg glargine, isophane) once daily (refer to Appendix H.1. Guide to starting and adjusting basal insulin).
  • Premixed (biphasic) insulin (eg lispro/lispro protamine or aspart/protamine insulin) once daily before the largest meal of the day143 (refer to Appendix H.2. Guide to starting and adjusting premixed insulin).

One way to commence insulin therapy is with basal insulin, which has a slightly lower risk of nocturnal hypoglycaemia, especially if the fasting glucose is consistently above target.105,141,143 Alternatively, premixed insulin may be more appropriate and simpler for a patient where fasting and postprandial glucose are consistently elevated.

Dosage adjustment can be more complex with premixed insulins as both insulin components are adjusted simultaneously, increasing the risk of hypoglycaemia and weight gain compared with basal insulin.143–145

Oral glucose lowering medications (eg metformin, sulphonylureas) may be continued as:141

  • early cessation before blood glucose targets are achieved can result in significant hyperglycaemia
  • ongoing use can reduce weight gain
  • ongoing use allows a smaller insulin dose and can reduce the risk of hypoglycaemia or hyperglycaemia.

Titrating insulin

Set an individualised target (refer to Section 8.1. Glycaemic monitoring), then ‘start low and go slow’ to gain patient confidence and reduce the risk of hypoglycaemia.141

If insulin is commenced early, HbA1c targets can often be achieved with a oncedaily insulin dose. Blood glucose control may be achieved before the HbA1c is at target because HbA1c measures the BGL over the preceding three months. Careful discussion of the impact of insulin on weight management needs to accompany dose titration, as well as the effect of exercise, carbohydrate intake and timing of meals with insulin dosing.

Check HbA1c (three months):

  • Generally, if HbA1c is within target, then continue with the current schedule.132
  • If HbA1c is outside the target, further action may be required (Box 5).

Box 5. If HbA1c is outside target142


Look for hidden hyperglycaemia by checking BGL before and 2 hours after lunch and dinner. Structured blood glucose monitoring may assist with this If postprandial hyperglycaemia is identified, consider:141

  • changing preceding meal size or composition 
  • increasing activity after meals
  • adding an oral agent (eg acarbose, glucagon-like peptide-1 receptor agonist [GLP-1 RA], sodium glucose co-transporter 2 inhibitor [SGLT2i]
  • or dipeptidyl peptidase-4 inhibitor [DPP-4i]) if the patient is not already taking one
  • adding a prandial insulin dose (refer to ‘Insulin intensification’ below)

 

Insulin intensification – Choosing a second-line insulin schedule


If HbA1c is elevated despite achieving appropriate BGL, a second-line insulin schedule (insulin intensification) should be implemented based on the individual patient’s needs (Table 7).
 

Table 7. Patient considerations with insulin intensification

Considerations when setting targets

Lower target

Higher target

Willing to monitor blood glucose level (BGL) several times per day

+

-

Support from family and general practitioner (GP)

+

-

Physically and cognitively capable

+

-

Considerations when selecting a schedule

Basal plus/Basal + glucagon-like-peptide-1 receptor agonist (GLP1 RA)/Basal + sodium glucose co-transporter 2 (SGLT2) inhibitor/Basal + dipeptidyl peptidase-4 inhibitor (DPP-4i)

Basal Premixed bolus

Patient preference for fewest injections

+

 

+

Variable meal pattern

+

+

 

Variable daily routine

+

+

 

Better postprandial control required

+

+

±

Limited capacity (eg dexterity)

 

 

+

The preferred schedule is not the one with the most ‘+’, but one which best meets the specific patient needs.146,147

There are newer insulin-intensification strategies146 that can be implemented.Basal insulin may be intensified in the following ways:

  • Commence with the addition of a GLP-1 RA (eg twice daily exenatide). This strategy has the potential to improve HbA1c and postprandial BGL, while controlling weight gain and not markedly increasing the risk of hypoglycaemia.148 Introduction of the GLP-1 RA requires instruction on injection technique – this is usually slowly titrated from a starting dose over several weeks, to a stable twice daily or once daily routine depending on the choice of agents. Only twice daily exenatide is currently TGA and PBS listed for use in combination with insulin. Liraglutide, an alternative GLP-1 RA, is currently TGA but not PBS approved. Longacting (weekly) exenatide is now PBS-approved for use  in combination with oral agents but not insulin.
  • Use with a single daily oral dose of an SGLT2i. If commenced – improved glycaemia may require dose reduction of insulin at initiation by 10–20% of the total daily dose.
  • Use with a daily dose of an oral DPP-4i – some agents have TGA approval and Pharmaceutical Benefits Advisory Committee (PBAC) recommendations, and will soon be PBS-approved, for this indication.

Complex regimes of additions to premixed insulin and basal bolus insulin may require additional specialist endocrinology support and education because of insulin dose adjustment complexity.

Insulin intensification regimes:

  • Basal plus – where additional preprandial injection of short-acting insulin is added to basal insulin (Appendix H.3. Guide to basal plus insulin intensification schedules).
  • Premixed – where additional injections of premixed are added to meals – either two or three times a day, or, alternatively, basal insulin is switched to premixed insulins (Appendix H.2. Guide to starting and adjusting premixed insulin).
  • Basal bolus – where short-acting insulin injections are used before each meal in addition to basal insulin (Appendix H.3. Guide to basal plus insulin intensification schedules).

As Basal bolus involves the most number of injections and monitoring, it is typically the final strategy implemented.

When insulin intensification is initiated (eg multiple daily doses of insulin), metformin should be continued, but any remaining insulin secretagogues may need to be reviewed to minimise risk of hypoglycaemia.

Follow-up

The insulin schedule and dosing should be reviewed at each consultation. The insulin dosage may need to be reduced if the person adopts a healthier lifestyle and/or loses weight.


Diabetes Australian and RACGP logo's
 
  1. Lau AN, Tang T, Halapy H, Thorpe K, Yu CH. Initiating insulin in patients with type 2 diabetes. CMAJ 2012;184(7):767–76.
  2. Colagiuri S, Dickinson S, Girgis S, Colagiuri R. National evidence based guideline for blood glucose control in type 2 diabetes. Canberra: NHMRC, 2009.
  3. Holman RR, Farmer AJ, Davies MJ, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med 2009;361(18):1736–47.
  4. National Prescribing Service. Early use of insulin and oral antidiabetic drugs. Prescribing Practice Review 40. Surry Hills, NSW: NPS, 2008.
  5. Phillips P. KISS: ‘keep insulin safe and simple’. Part 1: initiating insulin in type 2 diabetes. Medicine Today 2007;8(3):23–34.
  6. Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract 2011;17 Suppl 2:1–53.
  7. Goudswaard AN, Furlong NJ, Rutten GE, Stolk RP, Valk GD. Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus. Cochrane Database Syst Rev 2004(4):CD003418.
  8. Phillips PJ. Insulin and type 2 diabetes – A simple guide to prevent ‘stuff ups’. Aust Fam Physician 2006;35(12):975–78.
  9. Barnett A, Begg A, Dyson P, Feher M, Hamilton S, Munro N. Insulin for type 2 diabetes: choosing a second-line insulin regimen. Int J Clin Pract 2008;62(11):1647–53.
  10. Fulcher G, Colagiuri S, Phillips P, et al. Insulin intensification for people with type 2 diabetes: A practical approach. Australasian Medical Journal 2010;3(12):808–13.
  11. Perfetti R. Combining basal insulin analogs with glucagon-like peptide-1 mimetics. Diabetes Technol Ther 2011;13(9):873–81.